Abstract
Exosome is an extracellular vesicle released from multivesicular endosomes and contains micro (mi) RNAs and functional proteins derived from the donor cells. Exosomal miRNAs act as an effector during communication with appropriate recipient cells, this can aid in the utilization of the exosomes in a drug delivery system for various disorders including malignancies. Differences in the miRNA distribution pattern between exosomes and donor cells indicate the active translocation of miRNAs into the exosome cargos in a miRNA sequence-dependent manner, although the molecular mechanism is little known. In this study, we statistically analyzed the miRNA microarray data and revealed that the guanine (G)-rich sequence is a dominant feature of exosome-dominant miRNAs, across the mammalian species-specificity and the cell types. Our results provide important information regarding the potential use of exosome cargos to develop miRNA-based drugs for the treatment of human diseases.
Highlights
Exosomes are extracellular vesicles, ranging in size from 40 to 150 nm in diameter, which are released from variety cell types by the exocytotic fusion of multivesicular bodies of the endosome with the plasma membrane [1]
Isolation and characterization of activated human T cell, human tumor cell, murine T cell- and murine macrophage-released exosomes hPBMCs were cultured for two weeks in medium supplemented with OKT3, RetroNectin, rIL2 and autologous plasma, and the proportion of CD4+ or CD8+ cells was determined by flow cytometry
In addition to the dominancy of CD8+ cell population, the 2-weeks cultured hPBMCs abundantly expressed tetraspanins (CD9, CD63, and CD81), T cell-related molecules (CD3, CD28, CD45, T cell receptor [TCR] αβ), and human leukocyte antigens (HLA class I and class II molecules), their-released exosomes exhibited the modest expression of CD4, CD8, CD9, CD45, and HLA class II molecules and the substantial expression of CD63, CD81, and HLA class I molecules by flow cytometric analysis of the mAbstained exosome/latex beads, while no expression of CD3, CD28, or TCRαβ was detected on the surface of the cultured human T cell-released exosomes (Fig 1D)
Summary
Exosomes are extracellular vesicles, ranging in size from 40 to 150 nm in diameter, which are released from variety cell types by the exocytotic fusion of multivesicular bodies of the endosome with the plasma membrane [1]. Proteins and lipids are the major components of exosome membranes. Proteins on the exosome membranes are thought to function as ligands for interactions with target cells. Various nucleic acids, including mRNAs and microRNAs (miRNAs), are found in the exosomal lumen [1,2]. Evidence suggests that miRNAs in exosome cargos are able to modulate appropriate neighboring cells or distant recipient cells [1,2,3], the exact molecular mechanisms of endocytosis and the specific interaction between exosomes and target cells is yet to be clarified. MiRNAs are small (17–24 ribonucleic acids), non-coding RNAs (located mainly within genomic introns) that regulate post-transcriptional gene silencing by binding to the 3’-.
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